The Human KDR/flk-1 Gene Contains a Functional Initiator Element That Is Bound and Transactivated by TFII-I

Wu, Yaxu; Patterson, Cam

doi:10.1074/jbc.274.5.3207

Cited by 32 publications

(31 citation statements)

References 47 publications

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“…Together, these data suggest that an additional protein component(s), including a Btk substrate, is likely to be required for Bright-dependent transcriptional activity. TFII-I enhances transcription of promoters that lack TATA boxes and regulates promoter activity of the T-cell receptor ␤ locus through interactions with an initiator element (9,37,60). Although some IgH gene promoters contain good consensus TATA boxes, the V1 heavy chain promoter used in this system is TATA-less (7).…”

Section: Discussionmentioning

confidence: 99%

Bruton's Tyrosine Kinase Regulates Immunoglobulin Promoter Activation in Association with the Transcription Factor Bright

Rajaiya

Hatfield

Nixon

et al. 2005

Molecular and Cellular Biology

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Bright (B-cell regulator of immunoglobulin heavy chain transcription) binding to immunoglobulin heavy chain loci after B-cell activation is associated with increased heavy chain transcription. Our earlier reports demonstrated that Bright coimmunoprecipitates with Bruton's tyrosine kinase (Btk) and that these proteins associate in a DNA-binding complex in primary B cells. B cells from immunodeficient mice with a mutation in Btk failed to produce stable Bright DNA-binding complexes. In order to determine if Btk is important for Bright function, a transcription activation assay was established and analyzed using real-time PCR technology. Cells lacking both Bright and Btk were transfected with Bright and/or Btk along with an immunoglobulin heavy chain reporter construct. Immunoglobulin gene transcription was enhanced when Bright and Btk were coexpressed. In contrast, neither Bright nor Btk alone led to activation of heavy chain transcription. Furthermore, Bright function required both Btk kinase activity and sequences within the pleckstrin homology domain of Btk. Bright was not appreciably phosphorylated by Btk; however, a third tyrosine-phosphorylated protein coprecipitated with Bright. Thus, the ability of Bright to enhance immunoglobulin transcription critically requires functional Btk.Bright (B-cell regulator of immunoglobulin [Ig] heavy chain transcription) is a B-cell-restricted transcription factor that binds specific A-T-rich sequences. The protein consists of an acidic amino-terminal domain, a DNA-binding A-T-rich interaction domain, a putative transactivation domain, and a protein interaction domain (18). The carboxyl-terminal domain of Bright currently has no assigned function. Bright was originally identified in an antigen-specific B-cell line, BCg3R-1d, as a mobility-shifted complex induced after stimulation with interleukin-5 (IL-5) and antigen (54). Binding sites for Bright were originally identified 5Ј of the basal promoter of the V1 S107 gene but also exist within the matrix association regions on either side of the intronic enhancer (53, 55). Bright binding to the 5Ј-flanking sequences of the V1 S107 variable heavy chain (V H ) promoter correlated with two-to sixfold increases in heavy chain mRNA levels in response to 55). Deletion of Bright binding sites flanking the V1 promoter resulted in lack of antigen-and IL-5-stimulated heavy chain transcription (55). Bright expression is tightly regulated in normal murine lymphocytes, occurring in pre-B cells and late stages of B-cell differentiation (58). However, Bright is not present in detectable amounts in immature B cells, suggesting that it may not play a role in maintenance of Ig expression (58). On the other hand, Bright activity is induced in B cells activated in response to lipopolysaccharide (LPS), CD40 ligand stimulation, and anti-CD38 (55, 59). These data suggest that Bright enhances Ig heavy chain transcription above basal levels following B-cell activation.Our earlier results revealed that Bruton's tyrosine kinase (Btk) associates with Brig...

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Section: Discussionmentioning

confidence: 99%

Bruton's Tyrosine Kinase Regulates Immunoglobulin Promoter Activation in Association with the Transcription Factor Bright

Rajaiya

Hatfield

Nixon

et al. 2005

Molecular and Cellular Biology

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“…TFII-I is a unique transcription factor, because it can function both as a basal factor and as an activator (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11). Consistent with these functional activities, it has been shown to bind a core promoter element, Inr, and various upstream elements apparently through distinct DNA binding domains (1, 4, 6 -11).…”

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confidence: 93%

Structure-Function Analysis of TFII-I

Cheriyath¹,

Roy

2001

Journal of Biological Chemistry

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The transcription factor TFII-I can bind specifically to several DNA sequence elements and is implicated in both basal and activated transcription. There are four alternatively spliced isoforms of TFII-I, all characterized by the presence of six I-repeats, R1-R6, each containing a potential helix-loop-helix motif implicated in protein-protein interactions. These isoforms exhibit both homomeric and heteromeric interactions that lead to nuclear localization. In this study we mapped two distinct regions in TFII-I that affect its DNA binding. Deletion of either of these regions led to abrogation of DNA binding and transcriptional activation from both the V␤ and c-fos promoters. The I-repeats, as expected, were capable of mediating homomeric interactions either individually or in combination. Unexpectedly, an additional homomeric interaction domain was found within the N-terminal end of TFII-I that includes a putative leucine zipper motif. These data suggest a model in which TFII-I undergoes regulated homomeric interaction mediated by both the N-terminal end and the I-repeats.

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“…Electrophoretic Mobility Shift Assay (EMSA)-EMSA was performed as previously described (21). The probe consisted of annealed synthetic 54-bp complementary oligonucleotides corresponding to Ϫ95 to Ϫ42 of the hET-1 5Ј-flanking sequence (13) or a portion of the aforementioned hET-1 5Ј flanking sequence corresponding to Ϫ95 to Ϫ67 (5Ј probe), Ϫ76 to Ϫ57 (middle probe), or Ϫ66 to Ϫ42 (3Ј probe) as shown in Fig.…”

Section: Methodsmentioning

confidence: 99%

Vezf1/DB1 Is an Endothelial Cell-specific Transcription Factor That Regulates Expression of the Endothelin-1 Promoter

Aitsebaomo¹,

Kingsley-Kallesen²,

Wu³

et al. 2001

Journal of Biological Chemistry

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Coordinated gene regulation within the vascular endothelium is required for normal cardiovascular patterning during development and for vascular homeostasis during adulthood, yet little is known about the mechanisms that regulate endothelial transcriptional events. Vascular endothelial zinc finger 1 (Vezf1)/DB1 is a recently identified zinc finger-containing protein that is expressed specifically within endothelial cells during development. In this report, we demonstrate that Vezf1/ DB1 is a nuclear localizing protein that potently and specifically activates transcription mediated by the human endothelin-1 promoter, in a Tax-independent manner, in transient transfection assays. Using a combination of deletion mutagenesis and electrophoretic mobility shift assays, a novel Vezf1/DB1-responsive element was localized to a 6-base pair (bp) motif, ACCCCC, located 47 bp upstream of the endothelin-1 transcription start site. Recombinant Vezf1/DB1 also bound to this sequence, and a 2-bp mutation in this element abolished Vezf1/DB1 responsiveness by the endothelin-1 promoter. Vezf1/DB1 could be identified with a specific antibody in nuclear complexes from endothelial cells that bound to this element. Regulation of endothelin-1 promoter activity by Vezf1/DB1 provides a mechanism for endothelin-1 expression in the vascular endothelium during development and to maintain vascular tone; Vezf1/DB1 itself is a candidate transcription factor for modifying endothelial cell phenotypes in order to appropriately assemble and maintain the cardiovascular system.

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The Human KDR/flk-1 Gene Contains a Functional Initiator Element That Is Bound and Transactivated by TFII-I

Cited by 32 publications

References 47 publications

Bruton's Tyrosine Kinase Regulates Immunoglobulin Promoter Activation in Association with the Transcription Factor Bright

Bruton's Tyrosine Kinase Regulates Immunoglobulin Promoter Activation in Association with the Transcription Factor Bright

Structure-Function Analysis of TFII-I

Vezf1/DB1 Is an Endothelial Cell-specific Transcription Factor That Regulates Expression of the Endothelin-1 Promoter

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